Creatine May Not Only Build Muscle, But Also Help Fight Cancer

Creatine is widely known as a supplement used by athletes and bodybuilders to improve strength and performance. Now, new research from UCLA suggests it may have another surprising role: helping the immune system mount a stronger attack against cancer. The study, published in iScience, found that creatine boosts the activity of dendritic cells, specialized immune cells that detect tumors and activate the killer T cells responsible for destroying cancer. The findings build on previous research from the same laboratory showing that creatine also enhances the function of cancer-fighting T cells.

Many of today's cancer immunotherapies are designed to activate killer T cells, but only about 20% to 40% of patients experience meaningful benefits. The UCLA team believes that improving the function of dendritic cells, which coordinate and direct those T cells, could make immunotherapy effective for more people. "Immunotherapy has shown remarkable promise, but it only works for a subset of patients," said Lili Yang, the study's senior author. "What this study shows is that creatine doesn't just help the T cells fighting cancer – it also energizes the entire infrastructure that supports and guides them."

To understand how creatine influences the immune system, researchers first examined the activity of metabolic genes in dendritic cells that had entered tumors in mice. They discovered that the gene responsible for producing the creatine transporter, a protein that carries creatine into cells, was much more active in tumor-infiltrating dendritic cells than in dendritic cells found in healthy tissue. The team then engineered dendritic cells that lacked the creatine transporter. Without the ability to take up creatine, the cells survived less effectively, became less active, and were far less capable of preparing T cells to recognize and attack tumors.

Researchers also tested whether increasing creatine levels could produce the opposite effect. Daily creatine injections in mouse models of melanoma significantly slowed tumor growth while increasing both the number and activity of dendritic cells that had entered tumors. Using metabolomics analyses, the scientists found that creatine supplementation increased intracellular ATP levels in dendritic cells, which serves as the primary energy source powering nearly every cellular process. The researchers compared creatine's role to that of a rechargeable battery, allowing dendritic cells to store and release energy as needed.

The team also explored creatine's effects on human immune cells. In laboratory experiments, creatine enhanced the activation of human monocyte-derived dendritic cells, which are commonly used to develop dendritic cell cancer vaccines. It also improved those cells' ability to stimulate human T cells against a cancer-associated target. The findings suggest that adding creatine during the production of dendritic cell vaccines could potentially make those therapies more effective.

Despite the encouraging findings, the researchers caution that the work remains at an early stage. The experiments were conducted in mice and human cells grown in the laboratory, not in cancer patients, so the results should not be interpreted as evidence that creatine supplements improve cancer treatment in people. Although creatine monohydrate has been widely used for decades and is generally considered safe when taken at recommended doses, the researchers stress that anyone receiving cancer treatment should consult their physician before adding any supplement to their routine. The next step will be prospective clinical trials to determine whether creatine supplementation can improve outcomes for patients undergoing cancer immunotherapy.